Study of Immunity at the Genital Mucosa of HIV-1 Infected and Healthy Women

NCT01715103 | Terminated DMC

• 2 other identifiers: ANRS VEP1MUCOVAC
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

Current knowledge on mucosa, especially genitals in women, however, remain inadequate, especially regarding defense mechanisms and possibilities for a vaccine to induce an active immune response at mucosal front door of the most pathogens. Induction of mucosal immune response has emerged as a research priority research prophylactic vaccine.The development of strategies to prevent sexual transmission of HIV-1 depends in part on an understanding of specific and innate immune mechanisms involved in this transmission. MUCOVAC is a feasibility study of the immunological and transcriptomic analysis of cervicovaginal samples of women infected or not infected with HIV-1. We also assess tolerance samples taken by cytobrush and cervicovaginal washings, efficiency and reproducibility of the sample by cytobrush and cervicovaginal lavage for transcriptomic analysis, measurement of cytokines by Luminex technology, quantification of IgG and IgA. In blood we will determine the phenotype of B cells and Tfh cell frequency (T follicular helper) and quantification of serum immunoglobulins and will perform a transcriptomic analysis of blood cells. Finally we will make correlations with the observed responses at the genital mucosa. This pathophysiological exploratory study will be performed in 20 women infected with HIV-1 and 20 healthy women recruited from two centers in France and will include a screening visit and two visits M0 and M1 during which mucous and blood samples will be performed. The results of the study will capitalize skills in biology mucosa, using powerful tools to assess mucosal immunological parameters.

Conditions

HIV Infected Women; Healthy Women Volunteers

Keywords

HIV infection; mucosa; immunological parameters; genital sampling; healthy women volunteers

Outcome Measures

Primary Outcomes (1)

• Acceptability, tolerance, Efficiency

  * Acceptability * Local tolerance of sampling (particularly for collection by cytobrush), bleeding (need for protection, abundance, frequency) leucorrhoea (frequency, amount, aspect), fever, pain, gynecological vaginal burns and general tolerance (fever, occurrence of pelvic infection). * Efficiency of collection by washing (Ig rate \> 1μg/ml) and quality of cells collected by cytobrush and of cell pellet from washes for a transcriptomic analysis (the quantity and quality of RNA: RIN (RNA integrity number) \> 5 and an amount of RNA 50\> ng)

  2 months

Secondary Outcomes (4)

• Concentration of antibodies in cervicovaginal samples

  Month 0 and month 1

• Concentration of cytokines in cervicovaginal samples

  month 0 and month 1

• Expression genomics in cervicovaginal specimens and whole blood

  month 0 and month 1

• B phenotypes and the frequency of Tfh cells in whole blood

  month 0 and month 1

Study Arms (2)

Healthy women volunteers

OTHER

Healthy women volunteers with vaginal swabs by washing and cytobrush

Procedure: vaginal swabs by washing and cytobrush

HIV-1 infected women

OTHER

HIV-1 infected women with vaginal swabs by washing and cytobrush

Procedure: vaginal swabs by washing and cytobrush

Interventions

vaginal swabs by washing and cytobrush PROCEDURE

vaginal swabs by washing and cytobrush

HIV-1 infected women; Healthy women volunteers

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Free, informed and signed consent
• Person affiliated or beneficiary of a social security system or the Universal Health Coverage
• Female
• No menopausal, aged 18 to 45 years,
• Under oral contraceptive or implant
• Urine pregnancy test negative
• HBsAg and HCV serology negative
• Cervicovaginal smear normal older than one year,
• Normal vaginal smear dated within one year
• For healthy women
• \* HIV serology negative
• For infected women
• HIV-1 infection checked by western-blot and/or the detection of HIV-RNA
• CD4+ T cells \>350/mm3 (several tests, since 6 months)
• Viral load \<40 copies/ml since 6 months

You may not qualify if:

• Significant history of vaginal pathology (malignancy, prolapse)
• Hysterectomy, conization
• History of abnormal Pap smear in the previous year (ASC-US, AG-US and LSIL and high grade according to Bethesda).
• Breakthrough bleeding;
• Clinical symptoms suggestive of genital infection within 10 days prior to the examination of the study,
• Antibiotic systemically within 10 days prior to the examination of the study,
• Immunosuppressive or immunomodulatory treatment in the last six months and corticosteroids (\> 20 mg / day for 5 days) in last 3 months
• Population called vulnerable (minors, persons under guardianship, or deprived of liberty by a judicial decision.

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

Study Sites (2)

Centre d'investigation clinique Cochin Pasteur (CIC1417)

Paris, 75 679, France

Location

Service des maladies infectieuses et tropicales

Saint-Etienne, 42055, France

Location

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Fréderic LUCHT, PU PH

  Service des Maladies Infectieuses et Tropicales,CIC-EC, CHU Saint Etienne

  PRINCIPAL INVESTIGATOR

• Odile LAUNAY, PU PH

  Centre d'investigation clinique Cochin Pasteur (CIC 1417), hôpital Cochin Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2012
• First Posted: October 26, 2012
• Study Start: July 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: January 1, 2015
• Last Updated: July 1, 2015

Record last verified: 2015-06

Locations

FR (2)